PROVIDED. During the past decade, genetically modified mice have increasingly been a source of many new cancer models that have helped elucidate pathways contributing to tumor development and progression. With the completion of the human and mouse genome sequences and the initiation of large-scale efforts to functionally annotate these genomes, this trend will continue to accelerate. Production of genetically modified mice requires highly specialized instrumentation and expertise not available in most labs. The mission of the Gene Targeting and Transgenics Resource is to ensure that investigators at RPCI have access to state-of-the-art transgenic mouse technologies, methods and animal models. The Resource Director and Resource Assistant provide guidance to investigators from the earliest planning stages of the project when constructs are designed to advanced stages of the project during phenotype analysis. Resource technicians perform the specialized ES cell and embryo manipulation methods to generate the genetically modified mice. The Resource has several core vectors that have been successfully used in the preparation of modified mice, and these vectors are freely distributed to users as needed. New Resource services include preparation of transgenic mice using BAG DMA, ES cell-based transgenesis, a DNA purification service, cryopreservation of mouse strains and custom tissue culture services. Also implemented over the last several years have been quality control initiatives such as testing of DMAs and media for toxicity and testing of cell lines for contaminants and integrity. To date, the Resource has provided 516 new genetically modified lines (79 knockouts and 437 transgenics from 165 constructs) for four CCSG Programs. It also has assisted in the development of unique mouse models that contribute to understanding imprinting and its role in cancer, regulation of important genes and two transgenic models that mimic chromosome rearrangements associated with specific human cancers. Use of the Resource has continued to increase with the ongoing recruitment into the Genetics, Cell Stress and Biophysical Therapies, Prostate and Molecular Targets and Experimental Therapeutics Programs and projects requiring the development of transgenic mouse models. Increased usage of the Resource is expected to continue. The Resource is used by four Programs and 55% of users are CCSG members. $36,596 in CCSG support is requested, representing 13% of the total operating budget.